Role of microRNAs in the age-associated decline of pancreatic beta cell function in rat islets.

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Serval ID
serval:BIB_380DB5121536
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Role of microRNAs in the age-associated decline of pancreatic beta cell function in rat islets.
Journal
Diabetologia
Author(s)
Tugay K., Guay C., Marques A.C., Allagnat F., Locke J.M., Harries L.W., Rutter G.A., Regazzi R.
ISSN
1432-0428 (Electronic)
ISSN-L
0012-186X
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
59
Number
1
Pages
161-169
Language
english
Abstract
AIMS/HYPOTHESIS: Ageing can lead to reduced insulin sensitivity and loss of pancreatic beta cell function, predisposing individuals to the development of diabetes. The aim of this study was to assess the contribution of microRNAs (miRNAs) to age-associated beta cell dysfunction.
METHODS: The global mRNA and miRNA profiles of 3- and 12-month-old rat islets were collected by microarray. The functional impact of age-associated differences in miRNA expression was investigated by mimicking the observed changes in primary beta cells from young animals.
RESULTS: Beta cells from 12-month-old rats retained normal insulin content and secretion, but failed to proliferate in response to mitotic stimuli. The islets of these animals displayed modifications at the level of several miRNAs, including upregulation of miR-34a, miR-124a and miR-383, and downregulation of miR-130b and miR-181a. Computational analysis of the transcriptomic modifications observed in the islets of 12-month-old rats revealed that the differentially expressed genes were enriched for miR-34a and miR-181a targets. Indeed, the induction of miR-34a and reduction of miR-181a in the islets of young animals mimicked the impaired beta cell proliferation observed in old animals. mRNA coding for alpha-type platelet-derived growth factor receptor, which is critical for compensatory beta cell mass expansion, is directly inhibited by miR34a and is likely to be at least partly responsible for the effects of this miRNA.
CONCLUSIONS/INTERPRETATION: Changes in the level of specific miRNAs that occur during ageing affect the proliferative capacity of beta cells. This might reduce their ability to expand under conditions of increased insulin demand, favouring the development of type 2 diabetes.
Pubmed
Web of science
Open Access
Yes
Create date
03/01/2016 16:16
Last modification date
20/08/2019 13:26
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